Renal expression of vascular endothelial growth factor in lupus nephritis in the pediatric age group

Background: Vascular endothelial growth factor (VEGF) plays a crucial role in preservation of renal functions and may also serve as a useful biomarker in monitoring the progression of lupus nephritis (LN). Objective: We thought to correlate VEGF expression in the kidney with renal histopathology in lupus nephritis to unveil its possible relation to disease activity and severity.Methods: We consecutively enrolled 15 patients with lupus nephritis and ten renal biopsy specimens from patients with cystic renal diseases as controls. The study measurements included SLEDAI, SLICC/ ACR damage index and BILAG renal score. Paraffin sections from renal biopsies were subjected to routine haematoxylin and eosin staining and Immunohistochemical staining for VEGF. Results: Among SLE patients, 7 (46.7%) showed mild expression of VEGF, 5 (33.3%) showed moderate while 3 (20%) had strong expression of the marker. On the contrary, the control samples (100%) revealed strong marker expression. All subjects with class IV and V lupus nephritis had mild renal expression of VEGF. Renal expression of VEGF had a significant positive correlation with serum creatinine and complement C3 levels. The 24 hours’ excretion of urinary proteins had a significant negative correlation with the renal expression of the marker. On the other hand, the activity indices and therapeutic modalities did not correlate with VEGF expression. Conclusion: This pilot study among pediatric cases of SLE revealed mild to moderate VEGF expression in most cases of proliferative LN. Further longitudinal studies are needed to investigate the consequences of this finding on the prognosis of the disease.Keywords: VEGF, SLE, renal biopsy, lupus nephritis

Electroneurophysiological evaluation in children and adolescents with collagen diseases

Background: Sensorimotor neuropathies have been reported in patients with known or suspected connective tissue disease. It is often difficult to diagnose early neuropathies, and the study of the peripheral neuromuscular system is often made difficult by symptoms resulting from pain in the joints and limitation of movement.Objective: We aimed to investigate the central and peripheral nervous systems involvement in patients with pediatric- onset SLE and juvenile rheumatoid arthritis through clinical assessment and neurophysiological studies (motor nerve conduction velocity (MNCV) of the tibial nerve bilaterally and somatosensory evoked potentials (SSEPs) of the median nerve bilaterally) and to study their relation to clinical data and laboratory investigations.Methods: Nineteen patients with SLE (mean age 14.47± 3.94 years)and fifteen JRA patients (mean age 13.39±3.9 years) were included in the study. Ten healthy, matched subjects served as the control group. In addition to clinical assessment, including complete neurological and psychiatric evaluation, different investigative tools needed for diagnosis as well as assessment of systemic involvement and the degree of activity, were implemented. Both patients and control groups were subjected to neurophysiological studies (Motor nerve conduction velocity (MNCV) of tibial nerve bilaterally and Somatosensory evoked potentials (SSEPs) of the median nerve bilaterally).Results: Definite manifestations of neuropsychiatric involvement attributable to SLE was diagnosed in 37% of SLE patients. Of the SLE patients, 10.5% had abnormal MNCV on the right side, while Erb-N13 interpeak latencies were prolonged in 10.5% and 31.5% of the median nerves studied on the right and left sides, respectively, and N13-N20 was prolonged in 21% and 31.5%, respectively. Neither hypertension nor renal involvement significantly affected the studied parameters; however, SLE patients with cutaneous vasculitis showed slower MNCV of tibial nerve and prolonged Erb-N13 intervals on both sides. Erb-N13 and N13-N20 (on the right side) were positively correlated to the disease activity index (SLE-DAI). Of the JRA patients, 6% had slowed nerve conduction of right tibial nerve, while the interpeak latencies of Erb-N13 were prolonged in 6.6% and 13.3% on the right and left sides, respectively and N13-N20 was prolonged in 6.6% and 20%, respectively. Erb- N13 (on the right side) was negatively correlated to the cumulative dose of steroids.Conclusion: Our study revealed that sensorimotor neuropathies are often more common than expected in patients with collagen disease. Early subclinical neuropathies may be difficult to diagnose where symptoms from joint pain may mask the diagnosis. Widespread vasculitis including  vasculitis of the vasa nervora may be the underlying pathology, which  stresses the value of steroids in treatment.Key words: Collagen disease- neuropathy- somatosensory evoked potentials

Ultrasonic Guided Insertion of Central Venous Catheter in Infants and Children

Background/Purpose: ultrasound is licensed for application of regional blocks and insertion of vascular access. We aimed to compare ultrasonic guided (USG) and anatomical landmark technique (ALT) for insertion of central venous catheter (CVC) as regard success rate and rate of complications in infants and children. Materials & Methods: eighty childen (age ranged from 1-5 y) were classified into 2 groups, anatomical landmark technique was used to insert CVC in group I and ultrasonic guided technique was used in group II. Number of trials, duration of the procedure, and rate of complications were recorded. Results: There was a significant increase in success rate of insertion in group II as compared to group I (p = 0.001). Number of trials showed significant decrease in group II as compared to group I (p<0.0001). Incidence of arterial puncture was significantly decreased in group II (p = 0.028). Duration of the procedure was 21.3 ± 0.05 min in group I, and 12.5 ± 0.3 min in group II, ( p<0.0001). Conclusion: Insertion of central venous catheter in children should be guided with ultrasonography to avoid complications and failure of the procedure.Index Word: CV line insertion, ultrasonography

The role of HUCB derived stem cells therapy in repair of renal damage and improvement of renal function in cisplatin induced acute renal failure in rats

Acute renal failure (ARF) is a common clinical problem with increasing incidence, serious consequences, unsatisfactory therapeutic options and enormous financial burden to society. The aim is to investigate the role of human umbilical cord blood (HUCB) derived mesenchymal (MSCs) and CD34+ hematopoietic stem cell therapy in repair of renal damage and improvement of renal function in cisplatin-induced ARF model. Forty four rats were divided into 4 equal groups. ARF was induced in 3 groups using cisplatin and was confirmed by an increase in serum urea and creatinine levels after 5 days. On the same day, 2 groups were injected via the tail vein by either MSCs (1x106 cells/rat) or CD34+ hematopoietic cells (5 x105 cells/rat). The third group received intravenous injection of phosphate buffer saline and served as positive control, while the last group was normal control. Renal functions were followed up every 4 days. Thirty-three days after initiation of cisplantin injection, rats were sacrificed, kidneys were extracted for histopathological and immunohistochemical examination for detection of human specific anti-vimentin monoclonal mouse anti body to investigate homing of HUCB stem cells into the damaged renal tissue. Treatment with MSCs and CD34+ cells significantly decreased both serum urea and creatinine induced by cisplatin administration with concomitant improvement in the degree of necrotic and degenerative changes. There was no significant difference in these parameters between MSCs and CD 34+ stem cells treated groups. There was positive reaction for human specific anti-vimentin in 88.9% of animals in MSCs treated rats versus 87.5% in CD34+ cells treated rats. HUCB derived CD 34+ and MSCs accelerate regeneration of renal tubular epithelial cells and lead to reduction of progressive renal injury in cisplatin-induced acute renal failure rats.Keywords: Acute renal failure; CD 34+ cells; Umbilical cord blood; Mesenchymal stem cell

Prognostic value of FOXP3 and TGF-b expression in both peripheral blood and lymph nodes in patients with B-Non Hodgkin’s lymphoma

Foxp3 has been studied as a biomarker of Treg cells in many solid malignant diseases, although its role as an immunomodulator in B-NHL remain poorly understood and the effect of traditional chemotherapy on its expression remains unclear. In this study the role of circulating and intra-tumoral Treg and TGF-b in patients with B-NHL before and after chemotherapy was evaluated. Enumeration of Treg cells was carried out by flow cytometric staining of their cell surface markers CD4 and CD25 as well as by molecular analysis of its signature transcription factor FoxP3. Expression of FoxP3 was done using quantitative real-time PCR while TGF-b mRNA expression was semi-quantitatively assayed by the conventional reverse transcription-PCR. In addition, spontaneous versus mitogen-induced release of TGF-b by PBMCs was assessed by a short term cell culture followed by ELISA. This was done before and after six cycles of CHOP chemotherapy. The results were evaluated in relation to the clinicopathological data.A significant increase in mRNA transcripts of both Fox P3 and TGF-b as well as the percentage of CD4+/CD25+ in B-NHL patients before receiving the chemotherapy were recorded, when compared either to healthy controls or to patients after completion the treatment regimen. Interestingly 6 cycles of CHOP treatment caused significant reduction in all parameters under study, relative to the situation before treatment. A significant enhancement in spontaneous TGF-b release in B-NHL patient either before or after chemotherapy was obtained. These results strongly confirm the possible involvement of Treg cells and TGF-b in orienting the clinical course of the disease as well as the ability of targeting them in immunotherapeutic approaches. KEYWORDS FOXP3; TGF; Non Hodgkin’s lymphoma; NH

Storing cork oak (Quercus suber) seeds under different temperatures and the effect of storage treatments on the germination and growth of stored seeds

The cork oak "Quercus suber L." is one of the most important forest trees in the world, especially in the Mediterranean Basin, due to its high environmental, socioeconomic, and landscape value throughout the year. In general, these trees face particular problems that affect their germination, growth, survival, and  the other biotic and abiotic causes that affect natural regrowth.Thus, the most important of these problems is the annual irregularity in tree seed production. For this reason, The storage problems of this species are of concern to managers, who are using new alternative techniques to deal with the problem of the irregular annual production of oak seeds and to preserve them for as long as possible. The present work aimed to evaluate the effect of storing cork oak Quercus suber  L. seeds at different temperatures and for different periods of up to 300 days on their vitality and ability to germinate.  For this, the seeds were subjected to four storage parameters at four temperature levels: -0.5°C, -1°C, +4°C with thermotherapy, and +4°C without thermotherapy as a control from January 2019 to September 2019. Analysis of the obtained results showed that the treatments studied significantly affected the measured parameters. After 30 and 60 days, the results of the 4 treatments concluded that the fourth storage treatment (storage of seeds directly at +4°C) presented a good performance in terms of the length of the seedlings, which was high (52.45 cm), the production of seedlings with an average diameter of 5.28 mm, and the important germination percentage (88.57%), unlike the other treatments. After a storage period of 270 days, the fourth storage treatment, the control, stored at 4°C without thermotherapy, still showed the best growth and development. This treatment also achieved a higher germination percentage (17.14%), plant height (11.33cm), and average diameter (1.85 mm) than the other treatments.

Multiclass Semi-Supervised Learning on Graphs using Ginzburg-Landau Functional Minimization

We present a graph-based variational algorithm for classification of high-dimensional data, generalizing the binary diffuse interface model to the case of multiple classes. Motivated by total variation techniques, the method involves minimizing an energy functional made up of three terms. The first two terms promote a stepwise continuous classification function with sharp transitions between classes, while preserving symmetry among the class labels. The third term is a data fidelity term, allowing us to incorporate prior information into the model in a semi-supervised framework. The performance of the algorithm on synthetic data, as well as on the COIL and MNIST benchmark datasets, is competitive with state-of-the-art graph-based multiclass segmentation methods.Comment: 16 pages, to appear in Springer's Lecture Notes in Computer Science volume "Pattern Recognition Applications and Methods 2013", part of series on Advances in Intelligent and Soft Computin

T cell immunomodulation by clinically used allogeneic human cancellous bone fragments: a potential novel immunotherapy tool

Multipotential stromal cells (MSCs) demonstrate strong immunomodulation capabilities following culture expansion. We have previously demonstrated that human cancellous bone fragments (CBFs) clinically used as viable allografts for spinal fusion have resident MSCs that exhibit T cell immunomodulation after monolayer expansion. This study investigated the immunomodulatory ability of these CBFs without MSC culture-expansion. CD4 positive T cells were induced to proliferate using CD3/CD28 stimulation and added to CBFs at diferent ratios of T cells per gram of CBF. A dosedependent suppressive efect on T cell proliferation was evident and correlated with increased culture supernatant levels of TGF-ß1, but not PGE2. CBF-driven immunosuppression was reduced in co-cultures with TGF-ß neutralising antibodies and was higher in cell contact compared to non-contact cultures. CBF gene expression profle identifed vascular cell adhesion molecule-1, bone marrow stromal antigen 2/CD317 and other interferon signalling pathway members as potential immunomodulatory mediators. The CD317 molecule was detected on the surface of CBF-resident cells confrming the gene expression data. Taken together, these data demonstrate that human clinically used CBFs are inherently immunomodulatory and suggest that these viable allografts may be used to deliver therapeutic immunomodulation for immune-related diseases

Prostaglandin insert dinoprostone versus trans-cervical balloon catheter for outpatient labour induction: a randomised controlled trial of feasibility (PROBIT-F)

Background The aim was to assess the feasibility of conducting a randomised controlled trial (RCT) of induction of labour comparing use of two methods in the outpatient setting. Methods An open-label feasibility RCT was conducted in two UK maternity units from October 2017 to March 2019. Women aged ≥ 16 years, undergoing induction of labour (IOL) at term, with intact membranes and deemed suitable for outpatient IOL according to local guidelines were considered eligible. They were randomised to cervical ripening balloon catheter (CRB) or vaginal dinoprostone (Propess). The participants completed a questionnaire and a sub-group underwent detailed interview. Service use and cost data were collected via the Adult Service Use Schedule (AD-SUS). Women who declined to participate were requested to complete a decliners’ questionnaire. Results During the study period, 274 eligible women were identified. Two hundred thirty (83.9%) were approached for participation of whom 84/230 (36.5%) agreed and 146 did not. Of these, 38 were randomised to Propess (n = 20) and CRB (n = 18). Decliner data were collected for 93 women. The reasons for declining were declining IOL (n = 22), preference for inpatient IOL (n = 22) and preference for a specific method, Propess (n = 19). The intended sample size of 120 was not reached due to restrictive criteria for suitability for outpatient IOL, participant preference for Propess and shortage of research staff. The intervention as randomised was received by 29/38 (76%) women. Spontaneous vaginal delivery was observed in 9/20 (45%) women in the dinoprostone group and 11/18 (61%) women in the CRB group. Severe maternal adverse events were recorded in one woman in each group. All babies were born with good condition and all except one (37/38, 97.4%) remained with the mother after delivery. No deaths were recorded. − 21% of women in the dinoprostone group were re-admitted prior to diagnosis of active labour compared to 12% in the CRB group. Conclusions A third of the approached eligible women agreed for randomisation. An RCT is not feasible in the current service context. Modifications to the eligibility criteria for outpatient IOL, better information provision and round the clock availability of research staff would be needed to reach sufficient numbers